The goal of this program is to develop accelerator mass spectrometry (AMS) as an analytical tool for cancer research, specifically for tracing the interactions of carcinogens and cancer chemotherapeutic drugs with their biomolecular targets. AMS is a highly selective means for detecting and quantifying 14C in labeled biological samples, achieving a measurement sensitivity up to seven orders of magnitude greater than decay counting. Using AMS, 14C tracer studies may be conducted with less administered isotope and with smaller samples containing lower concentrations of isotope than previously possible. Newton Scientific, Inc. and collaborators at the Massachusetts Institute of Technology have developed a compact, low-energy AMS system designed specifically for analysis of biomedical samples. This instrument incorporates a unique continuous-flow interface that allows direct introduction of volatile organic compounds as well as gaseous CO2. The AMS instrument has been interfaced to a standard gas chromatograph, and the development of a liquid chromatograph interface is ongoing. Samples can also be introduced into the AMS as CO2 obtained from off-line oxidation of tissue samples. Phase I of this program is dedicated to bringing the recently constructed AMS instrument to the operational level required for use in tracer studies of carcinogens and chemotherapeutic agents and to using the instrument in proof-of-principle experiments with model compounds. In Phase II, we expect to undertake pilot studies in an ongoing anti-cancer drug development effort at MIT. PROPOSED COMMERCIAL APPLICATION: The biomedical 14C-AMS system used in this program will have widespread commercial applications in the molecular analysis of cancer. With this instrument, it will be possible to conduct studies of carcinogens, mutagens, toxins, and cancer therapeutics using many orders-of-magnitude less tracer activity than is possible today. A potentially important application of AMS is in the area of new durg research. The cost, size and operating requirements of the complete biomedical AMS system will be compatible with installation at major biomedical research centers.